Pernicious anemia in black people, is little known. Through this study we assess its diagnostic and evolutive aspects, and compare vitamin therapy B12 intramuscular and oral. Sixty six Biermer disease patients followed (January 2000-June 2014) at Internal Medicine Department of Aristide Le Dantec University Teaching Hospital (Senegal) are included. They were 26 men and 46 women (gender ratio: 0.65), who had a mean age of 47.84 years ± 15.25 years. Patients consulted for anemia (65 cases), acquired melanodermia (36 cases), gastrointestinal symptoms (30 cases), peripheral neuropathy (27 cases), venous thrombosis (2 cases), acute depression (1 case). Macrocytosis was observed in 52 cases. The mean hemoglobin in the vitamin B12 intramuscular group (52 patients) or oral group (14 patients) was the inclusion: 6.55 g/dl ± 3.12 g/dl vs 6.52 g/dl ± 2.18 g/dl (p = 0.04); and at day 8 treatment: 8.69 g/dl ± 2.49 g/dl vs 8.85 g/dl ± 1.9 g/dl (p = 0.43). Neurological and vascular presentations are unusual in contrast to macrocytic anemia. Oral administration of vitamin B12, simple and effective should be recommended in country with limited resources.
Biermer disease or pernicious anemia is a chronic auto-immune disease responsible for a chronic gastritis and a vitamin B12 deficiency, reversible under vitamin B12 therapy which oral administration is validated [
It is a retrospective, descriptive study with analytical outlook conducted upon comprehensive enrollment of medical files of Biermer disease patients followed from 1st January 2000 to 30th June 2014. The study held at Internal Medicine Department of superior referral hospital of Aristide Le Dantec University Teaching Hospital (Senegal) which has consultation, hospitalization and research activities. Our study included 66 files of Biermer disease, onto an annual average of 685 inpatients and 14,871 outpatients at Internal Medicine Department.
The diagnosis of Biermer disease was made in the presence of positive anti-intrinsic factor or anti-parietal cells antibodies, associated or not with vitamin B12 deficiency and atrophic gastritis [
Positive anti-intrinsic factor and anti-parietal cells antibodies were defined by measurements higher than 1.53 and 40 AU/ml respectively. Upper gastro-intestinal-tract (GIT) endoscopy with systematic antrum and fundusbiopsies and histology revealed gastric atrophy, metaplasia and helicobacter pylori (HP).
Cyanocobalamine is administered intramuscularly (1000 µg once a day for the 1st week, then once a week for a month and once a month for life) or orally (2000 µg per day for 10 days, followed by the same dose once a week for 4 weeks and then once a month for life). Indications for oral administration were: Ongoing anticoagulation, thrombocytopenia below 50,000/mm3 and difficult access to intramuscular injections. The median follow-up of patients treated with vitamin B12 (oral or intramuscular) was 1135.72, days [8 - 4886 days].
Statistic tests (medium, standard deviation, Student test) were done using Statistical Package for Social Sciences 20 software.
The files of 40 women and 26 men (gender ratio: 0.65), with mean age of 47.84 years ± 15.25 were included.
Comorbidities were metrorrhagia (2 cases), hemorrhagic cystitis (1 case) and partial gastrectomy for a benign tumour (1 case), vitiligo (5 cases), type 2 diabetes mellitus, Hashimoto thyroiditis (2 cases) and multiple auto immune disease syndrome (2 cases).
In 28 medical files blood group was specified and it was O (12 cases), A (7 cases), B (7 cases) and AB (2 cases)
Mean diagnostic time was 16 months (6 - 48 months). Presenting symptoms (
Clinical signs on diagnosis | n/N = 66 | (%) |
---|---|---|
Anemia manifestations | ||
Anemic syndrome | 40 | (60.6) |
Hemolytic anemia | 13 | (19.7) |
Anemic heart disease | 7 | (10.6) |
Isolated conjunctiva pallor | 5 | (7.6) |
GIT manifestations | ||
Epigastric pain | 30 | (45.5) |
glossitis | 21 | (31.8) |
diarrhea | 6 | (9) |
constipation | 4 | (6) |
dysphagia | 3 | (4.5) |
Dermatologic manifestations | ||
melanodermia | 36 | (54.5) |
Neuropsychiatric manifestations | ||
polyneuropathy | 27 | (40.9) |
posterior cord syndrom | 1 | (1.5) |
Acute depression | 1 | (1.5) |
Venous manifestations | ||
Saphenous and femoral thrombophlebitis | 1 | (1.5) |
Portal vein thrombosis incidentally discovered | 1 | (1.5) |
Paraclinical signs | n/N | (%) |
Anemia | 65/66 | (98.5) |
Thrombocytoenia | 33/66 | (50) |
Leukocytopenia | 29/66 | (43.9) |
Pancytopenia | 25/66 | (37.9) |
Bicytopenia | 18/66 | (27.3) |
Thrombocytosis | 2/66 | (3) |
Hyperleukocytosis | 1/66 | (1.5) |
Vitamin B12 deficiency | 59/66 | (89.39) |
Central megaloblastosis | 37/47 | (88.1) |
Positive anti-intrinsic factor antibodies | 50/51 | (98.03) |
Positive anti-parietal cells antibodies | 25/36 | (69.44) |
Atrophic gastritis | 34/37 | (91.89) |
Antrum and pyloric metaplasia | 10/37 | (27.02) |
Helicobacter pylori | 2/37 | (5.4) |
N: Total number of patients who did the test; n: Number of patients with abnormalities; %: Percentage.
cases), GIT signs including Hunter glossitis (21), polyneuropathy (27 cases) which one posterior cord syndrom, acute transient depression (1 case) and deep venous thrombosis (2 cases). The discovery of the disease was incidental in one patient who only had macrocytosis with no anemia (1).
Blood count (BC) (
Parameters | Beginning of the study | Mean | SD Extreme | ||
---|---|---|---|---|---|
D0: Hb (g/dl) | 6.52 | 2.93 | [1.3 - 15.2] | ||
MCV (fl) | 107.04 | 11.36 | [81 - 131] | ||
MCTH | 34.4 | 5.04 | [22 - 42.06] | ||
PLT (G/L) | 148.31 | 487.44 | [170 - 488] | ||
WBC (G/L) | 4.39 | 2.17 | [1.5 - 15.10] | ||
Ret. count (G/L) | 30.89 | 29.24 | [2 - 98] | ||
According to the route of administration of vitamin B12 | p¥ | ||||
Intramuscular (N = 52) | (n) Mean SD | Oral (N = 14) | (n) Mean SD | ||
D0: Hb (g/dl) | (52) 6.55 | 3.12 | (14) 6.52 | 2.18 | 0.43 |
MCV (fl) | 106.06 | 11.76 | 110.66 | 9.21 | 0.09 |
Ret. count (G/L) | 55.26 | 29.78 | 49.29 | 28.74 | 0.37 |
D8: Hb (g/dl) | (52) 8.69 | 2.49 | (14) 8.85 | 1.9 | 0.83 |
MCV (fl) | 100.03 | 10.72 | 99.53 | 8.51 | 0.89 |
Ret. count(G/L) | 104.65 | 102.78 | 145.52 | 87.39 | 0.27 |
M1: Hb (g/dl) | (41) 10.83 | 2.23 | (12) 11.81 | 1.16 | 0.16 |
MCV (fl) | 94.0 | 13.34 | 90.91 | 6.81 | 0.18 |
Ret. count(G/L) | 149.58 | 130.70 | 212.21 | 79.71 | 0.22 |
M6: Hb (g/dl) | (23) 12.71 | 1.89 | (12) 13.33 | 1.02 | 0.96 |
MCV (fl) | 86.02 | 8.60 | 86.14 | 8.28 | 0.97 |
Ret count (G/L) | 213.76 | 102.32 | 297.00 | 54.76 | 0.04 |
N: total number of patients treated, n: number of patients explored; Hb: hemoglobin; MCV: Mean Corpuscular Volume; Ret Count: reticulocyte count; SD: Standard deviation; Mean: Mean value; D0: Day 0 on admission; D8: Day 8; M1: 1st month; M6: 6th month; p¥: Student test.
cases) and hypochromia (4 cases). One patient had isolated macrocytosis at 115fl with hemoglobin of 15.2 g/dl. The mean hemoglobin was 6.52 g/dl ± 2.93 g/dl was below 6 g/dl in 47.7% of patients. BC (
In addition to BC abnormalities, we found megaloblastosis (88.7%), positive anti intrinsic factor (98.03%) and anti parietal cells antibodies (69.40%), atrophic gastritis (91.89%) and HP infection (5.4%) (
Overall evolution after intramuscular (52 cases) or oral (14 cases) vitamin therapy B12 is favorable. On day eighth, is observed a mean reticulocytosis crisis of 119.63 G/L ± 97.94 G/L [36 to 466.46 G/L]. Hemoglobin levels is rising during vitamin B12 administration (
and after 1 year the improvement was at 91.7% of patients.
In analytical study the mean hemoglobin level on vitamin B12 supplements in the intramuscular group versus oral, was on day eight 8.69 ± 2.5 g/dl Vs 8.85 ± 1.9 g/dl (p = 0.43) and after 1 month it was 10.83 ± 2.2 g/dl Vs 11.81 ± 1.1 g/dl (p = 0.16) (
The available literature on Biermer disease in sub-Saharan Africa is made of limited series.
In 2003, Segbenaet al [
In our study as well as in other african publications [
In our study, anemia signs are predominantly made of anemic syndromefar ahead of hemolytic anemia and anemic heart disease. Heart failure as described in our patients is a chronic complication of cardiovascular manifestations common to all vitamin B12 deficiencies as described in almost 50% of cases by Nafil et al. [
Acquired melanodermia, second presenting sign in our study is also frequently reported in African publications [
The third diagnostic condition in our study was GIT signs with atypical epigastric pain, followed by Hunter glossitis. This one is more specific of Biermer disease and was noted in 78.57% of patients in Diop et al. series [
The least observed manifestation in our patients was deep venous thrombosis. As a comparison Zulfiquar et al. [
Beside thrombosis, acute depression and combined sclerosis of the bone marrow are rare in our study (1 case) like in the literature [
Main BC abnormalities were macrocytic anemia followed by thrombocytopenia and neutropenia both in our patients and in Song and al series [
Characteristic bone marrow aspirate findings in our study were the high frequency of megaloblastosis, coinciding with results of de Segbena et al. [
Positive anti-intrinsic factor antibody which is more specific of the disease [
Prevalence of atrophic gastritis was high unlike HP surinfection which was rare. Similar findings in this regard were also obtained by Wun Chun et al. [
On therapeutic aspect, hematologic abnormalities are reversible with vitamin B12 treatment, more frequently administered intramuscularly in our study and in the literature [
Oral route of administration is effective and is indicated in case of severe thrombocytopenia or anticoagulation treatment [
Macrocytic anemia and acquired melanodermia are frequently revealing sign of Biermer disease, in contrast to neuropyschiatric and vascular manifestations. Oral route of vitamin B12 administration, simple and equally effective should be strongly promoted in sub-Saharan Africa regions with limited resources.
Fall, S., Diagne, N., Diop, O.-D., Djiba, B., Ndiaye, F.-S.-D. and Pouye, A. (2016) Biermer Disease: Initial Presentation and Follow-Up of 66 Patients in Internal Medicine Department in Senegal. International Journal of Clinical Medicine, 7, 585-591. http://dx.doi.org/10.4236/ijcm.2016.79064